April 4, 2022: “In the XARENO study, after a minimum follow up period of one year, Xarelto (rivaroxaban) was associated with a greater net clinical benefit (lower event rates for stroke and other thromboembolic events, major bleeding and all-cause mortality) and a reduced risk of kidney failure in patients with non-valvular atrial fibrillation (NVAF) and advanced chronic kidney disease (CKD) compared to vitamin K antagonists.
The study findings were presented at the American Congress of Cardiology’s 71st Annual Scientific Session (ACC.22).
“Chronic kidney disease is a common and potentially deadly condition that is widely underrecognized, despite the fact it can severely impact patients’ quality of life,” said Reinhold Kreutz, Professor of Clinical Pharmacology, Charité University – Medicine Berlin.
“The XARENO study findings provide important evidence that can help physicians in the management of patients with atrial fibrillation and chronic kidney disease and help reduce patients’ risk of progressing to kidney failure.”
XARENO is the first prospective observational study to evaluate the effectiveness and safety of Xarelto versus VKAs or no oral anticoagulation (at the discretion of attending physicians) in treating patients with NVAF and advanced CKD.
The prevention of worsening renal function is an important additional therapeutic target beyond stroke prevention when it comes to the selection of an oral anticoagulant in patients with atrial fibrillation (AF).
The XARENO study was undertaken to investigate the real-world effectiveness and safety of Xarelto compared with VKAs in this vulnerable patient group with AF and advanced CKD.
The study adds to the evidence obtained in the randomized controlled ROCKET-AF study and supports the use of Xarelto in this patient group including patients with CKD stage 4.
In agreement with previous data demonstrating various benefits of rivaroxaban over VKAs on kidney outcomes, XARENO also suggests a potential reduction in kidney failure of Xarelto vs VKA.
With XARENO and previous studies like ANTENNA Xarelto provides the broadest evidence on preservation of renal function compared to all other NOACs.
“Previous trials evaluating stroke prevention in atrial fibrillation have excluded patients with advanced chronic kidney disease. Consequently, the clinical impact of NOACs versus VKAs in this patient population was unknown,” said Dr. Mike Devoy, Chief Medical Officer and Head of Medical Affairs and Pharmacovigilance for the Pharmaceuticals Division at Bayer. “The XARENO study provides crucial new insights into how we can help to prevent disease progression and improve clinical outcomes in people with atrial fibrillation and chronic kidney disease.”
About atrial fibrillation (AF) and chronic kidney disease (CKD)
AF is the most common sustained cardiac rhythm disorder. In AF, the upper chambers of the heart (atria) contract irregularly.
As a result, blood does not flow properly, potentially allowing blood clots to form. These blood clots can break loose and travel to the brain, resulting in a stroke.
Patients with AF can have a up to 5 times higher risk of stroke than those without AF. AF is frequently associated with comorbidities, including CKD.
It’s estimated that 15–20% of people with AF also have CKD. CKD is a common and potentially deadly condition that is widely underrecognized.
The disease progresses silently and unpredictably, with many symptoms not appearing until CKD is well-advanced. CKD is one of the most frequent complications arising from diabetes and is also an independent risk factor of cardiovascular disease.
Previous studies have found that patients with both AF and renal impairment are at higher risk for bleeding and stroke. They are also more likely to be undertreated with oral anticoagulation such as warfarin than those with normal renal function.
About XARENO
The XA inhibition in RENal patients with non-valvular atrial fibrillation Observational registry (XARENO) was a prospective, non-interventional, international multicenter study recruiting AF patients with CKD in five European countries.
The results build on findings from a retrospective database analysis which indicated that Xarelto may be associated with lower risks of adverse renal outcomes in patients with CKD and NVAF, compared with VKA.
Between April 2016 and January 2020, 1,550 patients were enrolled in the study. Patients treated with Xarelto or VKA having estimated glomerular filtration rates (eGFR) between 15 and 49 mL/min per 1.73 m2 were eligible for inclusion.
Patients without anticoagulation at the discretion of the attending physicians were also enrolled for explorative analysis.
The study population comprised 766 patients in the Xarelto group, 695 in the VKA group, and 89 in the group without anticoagulation and 85 patients not eligible/with missing information.
Patients were treated with either Xarelto or VKA at the discretion of the attending physicians. Pre-specified follow-up was at least 12 months with a planned extended data collection period for one up to two additional years.
Primary outcomes, as determined by blinded adjudication, included progression of CKD and net-clinical benefit (stroke and other thromboembolic events, major bleeding, and all-cause mortality).
Propensity score matched analysis (PSMA) was used to compare the Xarelto and VKA groups.
After one year follow up, the study found that in PSMA, baseline eGFR was similar in both groups and numerically higher in the rivaroxaban group after follow-up (difference 1.0 mL/min per 1.73 m2, 95% confidence interval [CI] -0.48 to 2.51, p=0.18).
The frequency of net-clinical benefit events was 12.9% (51/397) in the rivaroxaban and 18.3% (75/410) in the VKA group (incidence rate ratio [IRR] 0.68, 95% CI 0.47 to 0.96, p=0.03).
The incidence risk ratio (IRR) for progression to CKD stage 5 was 0.40 (CI 0.22 to 0.71) and the IRR for in the initiation of chronic renal replacement therapy was 0.08 (CI 0.01 to 0.63).
About Rivaroxaban (Xarelto™)
Rivaroxaban is the most broadly indicated non-vitamin K antagonist oral anticoagulant (NOAC) worldwide and is marketed under the brand name Xarelto. Xarelto is approved for more venous and arterial thromboembolic (VAT) conditions than any other NOAC:
· The prevention of stroke and systemic embolism in adult patients with non-valvular atrial fibrillation (AF) with one or more risk factors
· The treatment of pulmonary embolism (PE) in adults
· The treatment of deep vein thrombosis (DVT) in adults
· The prevention of recurrent PE and/or DVT in adults
· The prevention of venous thromboembolism (VTE) in adult patients undergoing elective hip replacement surgery
· The prevention of VTE in adult patients undergoing elective knee replacement surgery
· The prevention of atherothrombotic events after an Acute Coronary Syndrome in adult patients with elevated cardiac biomarkers when co-administered with acetylsalicylic acid (ASA) alone or with ASA plus clopidogrel or ticlopidine
· The prevention of atherothrombotic events in adult patients with coronary artery disease (CAD) or symptomatic peripheral artery disease (PAD) at high risk for ischemic events when co-administered with acetylsalicylic acid (ASA)
· Treatment of venous thromboembolism (VTE) and prevention of VTE recurrence in children and adolescents aged less than 18 years after at least 5 days of initial parenteral anticoagulation treatment
· Thromboprophylaxis (prevention of VTE and VTE related events) in children aged two years and older with congenital heart disease who have undergone the Fontan procedure
Xarelto is approved in more than 130 countries, although the approved labelling, including the number of indications may differ from country to country. Since launch in 2008, more than 100 million patients have been treated.
Rivaroxaban was discovered by Bayer and is being jointly developed with Janssen Research & Development, LLC. Xarelto is marketed outside the U.S. by Bayer and in the U.S. by Janssen Pharmaceuticals, Inc. (Janssen Research & Development, LLC and Janssen Pharmaceuticals, Inc. are part of the Janssen Pharmaceutical Companies of Johnson & Johnson).
Anticoagulant medicines are therapies used to prevent or treat serious illnesses and potentially life-threatening conditions.
Before initiating treatment with anticoagulant medicines, physicians should carefully assess the benefit and risk for the individual patient.
Responsible use of Xarelto is a very high priority for Bayer, and the company has developed a Prescribers Guide for physicians and a Xarelto Patient Card for patients to support best practice.”
